The synthesis of two classes (5-(X-benzyl)-2,4-diaminopyrimidines and 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3-X-phenyl)-s-triazines) of inhibitors of dihydrofolate reductase (DHFR) will continue. These inhibitors will be tested on various kinds of purified DHFR from murine and human tumors as well as DHFR from normal mammalian tissue. The inhibitors will also be tested against L-5178-Y tumor cells and, if time permits, against KB tumor cells. Any compound showing sensitivity will be tested against tumors in whole animals. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application.